Previous GeneCards Identifiers for VPS35 Gene

Summaries for VPS35 Gene

Entrez Gene Summary for VPS35 Gene

This gene belongs to a group of vacuolar protein sorting (VPS) genes. The encoded protein is a component of a large multimeric complex, termed the retromer complex, involved in retrograde transport of proteins from endosomes to the trans-Golgi network. The close structural similarity between the yeast and human proteins that make up this complex suggests a similarity in function. Expression studies in yeast and mammalian cells indicate that this protein interacts directly with VPS35, which serves as the core of the retromer complex. [provided by RefSeq, Jul 2008]

UniProtKB/Swiss-Prot for VPS35 Gene

Acts as component of the retromer cargo-selective complex (CSC). The CSC is believed to be the core functional component of retromer or respective retromer complex variants acting to prevent missorting of selected transmembrane cargo proteins into the lysosomal degradation pathway. The recruitment of the CSC to the endosomal membrane involves RAB7A and SNX3. The CSC seems to associate with the cytoplasmic domain of cargo proteins predominantly via VPS35; however, these interactions seem to be of low affinity and retromer SNX proteins may also contribute to cargo selectivity thus questioning the classical function of the CSC. The SNX-BAR retromer mediates retrograde transport of cargo proteins from endosomes to the trans-Golgi network (TGN) and is involved in endosome-to-plasma membrane transport for cargo protein recycling. The SNX3-retromer mediates the retrograde endosome-to-TGN transport of WLS distinct from the SNX-BAR retromer pathway. The SNX27-retromer is believed to be involved in endosome-to-plasma membrane trafficking and recycling of a broad spectrum of cargo proteins. The CSC seems to act as recruitment hub for other proteins, such as the WASH complex and TBC1D5 (Probable). Required for retrograde transport of lysosomal enzyme receptor IGF2R and SLC11A2. Required to regulate transcytosis of the polymeric immunoglobulin receptor (pIgR-pIgA) (PubMed:15078903, PubMed:15247922, PubMed:20164305). Required for endosomal localization of FAM21C (PubMed:22070227). Mediates the association of the CSC with the WASH complex via FAM21 (PubMed:22070227, PubMed:24980502, PubMed:24819384). Required for the endosomal localization of TBC1D5 (PubMed:20923837).

Flow Cytometry Products

Function for VPS35 Gene

Products:

Molecular function for VPS35 Gene

UniProtKB/Swiss-Prot Function: Acts as component of the retromer cargo-selective complex (CSC). The CSC is believed to be the core functional component of retromer or respective retromer complex variants acting to prevent missorting of selected transmembrane cargo proteins into the lysosomal degradation pathway. The recruitment of the CSC to the endosomal membrane involves RAB7A and SNX3. The CSC seems to associate with the cytoplasmic domain of cargo proteins predominantly via VPS35; however, these interactions seem to be of low affinity and retromer SNX proteins may also contribute to cargo selectivity thus questioning the classical function of the CSC. The SNX-BAR retromer mediates retrograde transport of cargo proteins from endosomes to the trans-Golgi network (TGN) and is involved in endosome-to-plasma membrane transport for cargo protein recycling. The SNX3-retromer mediates the retrograde endosome-to-TGN transport of WLS distinct from the SNX-BAR retromer pathway. The SNX27-retromer is believed to be involved in endosome-to-plasma membrane trafficking and recycling of a broad spectrum of cargo proteins. The CSC seems to act as recruitment hub for other proteins, such as the WASH complex and TBC1D5 (Probable). Required for retrograde transport of lysosomal enzyme receptor IGF2R and SLC11A2. Required to regulate transcytosis of the polymeric immunoglobulin receptor (pIgR-pIgA) (PubMed:15078903, PubMed:15247922, PubMed:20164305). Required for endosomal localization of FAM21C (PubMed:22070227). Mediates the association of the CSC with the WASH complex via FAM21 (PubMed:22070227, PubMed:24980502, PubMed:24819384). Required for the endosomal localization of TBC1D5 (PubMed:20923837).

UniProtKB/Swiss-Prot

Parkinson disease 17 (PARK17) [MIM:614203]: An autosomal dominant, adult-onset form of Parkinson disease. Parkinson disease is a complex neurodegenerative disorder characterized by bradykinesia, resting tremor, muscular rigidity and postural instability, as well as by a clinically significant response to treatment with levodopa. The pathology involves the loss of dopaminergic neurons in the substantia nigra and the presence of Lewy bodies (intraneuronal accumulations of aggregated proteins), in surviving neurons in various areas of the brain. {ECO:0000269 PubMed:21763482, ECO:0000269 PubMed:21763483, ECO:0000269 PubMed:22517097}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Publications for VPS35 Gene

Membrane recruitment of the cargo-selective retromer subcomplex is catalysed by the small GTPase Rab7 and inhibited by the Rab-GAP TBC1D5.(PMID: 19531583)Seaman M.N. … Bright N.(J. Cell. Sci. 2009)3423